1. Field of the Invention
This application relates to Microsystems for determining clotting time of blood and low-cost, single-use devices for use therein.
2. Background Art
The following references are referred to herein:                [1] D. G. Carville et al., “Coagulation Testing Part 2: The Quest to Optimize Near-Patient Analyzers,” IVD TECHNOLOGY MAGAZINE, September 1998.        [2] Walter Seegers ed., “Blood Clotting Enzymology,” ACADEMIC PRESS, New York, N.Y. 1967.        [3] Maxwell M. Wintrobe ed., “Blood, Pure and Eloquent,” MCGRAW-HILL BOOK CO., New York, N.Y. 1980.        [4] John F. Dailey, “Blood,” MEDICAL CONSULTING GROUP, Arlington, Mass., 1998.        [5] E. C. Albrittion ed., “Standard Values in Blood,” W. B. SANDERS CO., Philadelphia, Pa. 1952.        [6] Gottfried Schmer and Paul E. Strandijard, eds., “Coagulation Current Research and Clinical Applications,” ACADEMIC PRESS, New York, N.Y. 1973.        [7] G. W. Scott Blair, “An Introduction to Biorheology,” ELSEVIER SCIENTIFIC PUBLISHING CO., New York, N.Y. 1974.        [8] M. Kaibara, “Rheological Studies on Blood Coagulation and Network Formation of Fibrin,” POLYMER, GEL, AND NETWORKS, Vol. 2, No. 1, 1994, pp. 1-28.        [9] E. Hrncir et al., “Surface Tension of Blood,” PHYSIOLOGICAL RESEARCH, Vol. 46, No. 4, August 1997, pp. 319-321.        [10] A. Bard et al., “Electrochemical Methods,” JOHN WILEY AND SONS, New York, N.Y. 1980.        [11] V. F. Rusyaev, “Conductive Method of Studying Blood Coagulation,” BIOMEDICAL ENGINEERING, Vol. 21, No. 3, May-June 1987, pp. 114-118.        [12] L. E. Blake, “Principles of the Impedance Technique,” IEEE ENG. IN MEDICINE AND BIOLOGY MAGAZINE, Vol. 8, No. 1, March 1989, pp. 11-15.        [13] R. H. Olsson III et al., “Silicon Neural Recording Arrays with On-Chip Electronics for In-Vivo Data Acquisition,” IEEE-EMBS SPECIAL TOPIC CONFERENCE ON MICROTECHNOLOGIES IN MEDICINE AND BIOLOGY, pp. 237-240, May 2002.        [14] H. Lorenz et al., “High-Aspect Ratio, Ultrathick, Negative-Tone Near-UV Photoresist and its Applications for MEMS,” SENSORS AND ACTUATORS A: PHYSICAL, Vol. 64, No. 1, January 1998, pp. 33-39.        
In an effort to reduce health care costs, the medical industry has been moving away from centralized laboratories to point-of-care instrumentation and analysis. One such example is near-patient blood coagulation analyzers [1], including Technidyne Corp.'s Hemachron 8000 and Cardiovascular Dynamics Inc.'s TAS. Many different-diseases, including Hemophilia A and B, thrombocythmia, Christmas disease, and prothrombin deficiency, affect the in vivo coagulation of blood. Treatment of these diseases requires medication with either coagulants or anticoagulants like the industry standard heparin or tannin [2,3]. In order to ensure proper medication, at-home testing would be a great benefit for individuals suffering from these diseases. Near-patient blood testing during cardiac surgery is equally important because blood clotting must be monitored to ensure a successful operation. An accelerated clotting time (ACT) test is used in this situation to make sure the patient is properly heparinized [4].
Clearly there is a need for low-cost blood coagulation analyzers. Additionally, disposable, single-use devices are preferable so as to avoid autoclaving and other cleaning procedures.
Blood coagulation analysis is useful for determining proper medication for medical conditions such as hemophilia, liver disease, and cardiac surgeries and has many uses in laboratories, hospitals, and even at home.
The following is a brief list of some makers of blood coagulation analyzers, the product, name, and the detection scheme:                1. Helena Laboratories (http://www.helena.com) makes an instrument called the Actalyke. This device places a magnet in the blood and oscillates it back and forth detecting the rate of movement. The change in rate of movement detects coagulation.        2. i-STAT (http://www.istat.com) makes an instrument called the i-STAT. This device uses an indicator substance to detect hemocrit. This indicator is then sensed electrochemically.        3. Instrumentation Laboratories (http://www.ilus.com) makes an instrument called the GEM PCL. This device flows the blood past an optical window until the blood no longer passes indicating that it has clotted.        4. International Technidyne Corporation (http://www.itcmed.com) makes an instrument called the ProTime Microcoagulation System. This is intended to be an at-home test device. The coagulation is detected by pumping a precise amount of blood back and forth in a channel until it no longer flows.        5. Sienco, Inc. (http://www.uscid.org/˜sienco/) has an instrument called Sonoclot. Sonoclot works by placing a mechanical probe into the blood and mechanically resonating it back and forth. By detecting the resistance to motion changes, a determination of the blood's coagulation can be determined.        
The following are prior art U.S. patents related to blood clot sensors:
U.S. Pat. No. 5,039,617—McDonald et al describes capillary channels in plastic devices for measuring accelerated clotting time tests. Included in this patent are chambers for mixing the reagents needed for the ACT tests and methods for including the reagents. Optical or electromechanical techniques are used for detection of coagulation times.
U.S. Pat. No. 6,521,182—Shartle et al. A channel flow to a measurement area where optical transmittance is measured. A disposable cartridge-type device.
U.S. Pat. No. 5,504,011—Gavin et al. A channel-type device that requires pneumatic pumps to move fluid back and forth, thus recording its clotting time.
U.S. Pat. No. 5,908,786—Moreno et al. A long elongated channel with microheaters underneath. A thermionic compound is mixed with the blood and based on how far it flows into the channel, the color is changed and the results are read by the users like a litmus paper test.
U.S. Pat. No. 6,448,024 is an update of the McDonald et al. patent. The device is used to measure both clotting time and amount of fribrinogen by mixing in different compounds.
U.S. Pat. No. 4,797,369—Mintz. Blood is continuously brought together in a chamber and then separated. A fibrigen bridge is formed between the two solutions when clotting starts and this creates an electrical short between the two solutions.
Published U.S. patent application No. 0180824—Mpock. Mechanical components spin in the solution and periodically raise out of the blood. Clots form on the spinning arms and are detected optically.
U.S. Pat. No. 4,105,411—Biver. Handheld device which acts like a stopwatch with a built-in heater. Blood is in test tubes and the blood flows back and forth across an open window. The user visually looks for clots.
U.S. Pat. No. 4,125,327—Margolis. Plunger-type device that can add compounds into whatever solution one is measuring. Reaction changes are measured optically.
U.S. Pat. No. 4,876,069—Jochimsen. Metal stirrer or ball in the blood that creates turbidity. Clotting time is measured by measuring turbidity optically.
U.S. Pat. No. 4,964,728—Kloth et al. Describes similar mechanisms to U.S. Pat. No. 4,876,069.
U.S. Pat. No. 5,167,145—Butler et al. Uses infrared to measure composition changes in the blood as it clots.
U.S. Pat. No. 6,555,064—Baugh et al. Benchtop device that sends a plunger into a test-tube with blood in it. Clotting is measured by the rate of descent of the plunger.
U.S. Pat. No. 6,438,498—Opalsky et al., Measures chemical composition of the clots as they flow across a channel. Uses conductivity and amperometric sensors to measure composition.